NZ334340A - Tricyclic compounds that inhibits farnesyl protein transferase I but not geranylgeranyl protein transferase I in the treatment of cancer or cancer-like conditions - Google Patents
Tricyclic compounds that inhibits farnesyl protein transferase I but not geranylgeranyl protein transferase I in the treatment of cancer or cancer-like conditionsInfo
- Publication number
- NZ334340A NZ334340A NZ334340A NZ33434097A NZ334340A NZ 334340 A NZ334340 A NZ 334340A NZ 334340 A NZ334340 A NZ 334340A NZ 33434097 A NZ33434097 A NZ 33434097A NZ 334340 A NZ334340 A NZ 334340A
- Authority
- NZ
- New Zealand
- Prior art keywords
- alkyl
- group
- formula
- halo
- aryl
- Prior art date
Links
- 125000002686 geranylgeranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 title abstract 4
- 206010028980 Neoplasm Diseases 0.000 title abstract 3
- 102000004357 Transferases Human genes 0.000 title abstract 3
- 108090000992 Transferases Proteins 0.000 title abstract 3
- 150000001875 compounds Chemical class 0.000 title abstract 3
- 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 title abstract 2
- 201000011510 cancer Diseases 0.000 title 2
- 125000000217 alkyl group Chemical group 0.000 abstract 7
- 125000001475 halogen functional group Chemical group 0.000 abstract 5
- 125000003118 aryl group Chemical group 0.000 abstract 4
- -1 benzotriazol-1-yloxy, tetrazol-5-ylthio, substituted tetrazol-5-ylthio Chemical group 0.000 abstract 3
- 125000004432 carbon atom Chemical group C* 0.000 abstract 3
- 230000002159 abnormal effect Effects 0.000 abstract 2
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 2
- 230000010261 cell growth Effects 0.000 abstract 2
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 2
- 230000001131 transforming effect Effects 0.000 abstract 2
- IXAGRXJIXIPQDR-OWOJBTEDSA-N (e)-2-nitroethenamine Chemical group N\C=C\[N+]([O-])=O IXAGRXJIXIPQDR-OWOJBTEDSA-N 0.000 abstract 1
- 102000007317 Farnesyltranstransferase Human genes 0.000 abstract 1
- 108010007508 Farnesyltranstransferase Proteins 0.000 abstract 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000000304 alkynyl group Chemical group 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 238000004113 cell culture Methods 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 1
- 238000000338 in vitro Methods 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 230000003834 intracellular effect Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- 229940121649 protein inhibitor Drugs 0.000 abstract 1
- 239000012268 protein inhibitor Substances 0.000 abstract 1
- 229920006395 saturated elastomer Polymers 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
The use of compounds represented by formula I as farnesyl transferase protein inhibitors. The tricyclic compounds disclosed does not inhibit geranylgeranyl protein transferase I, in vitro, as it appears to block the phenotypic change induced by a form of transforming Ras engineered to be a geranylgeranyl acceptor, blocks intracellular processing of Ras which is a farnesyl acceptor but not of a Ras engineered to be a geranylgeranyl acceptor and it blocks abnormal cell growth in cell culture induced by transforming Ras. The pharmaceutical composition is useful for inhibiting abnormal cell growth, such as tumours. Wherein; One of a, b, c and d represents N or NR9 wherein R9 is O-, -CH3 or -(CH2)nCO2H wherein n is 1 to 3, and the remaining a, b, c and d groups represent CR1 or CR2; or a, b, c, and d are independently selected from the group consisting of CR1 and CR2; wherein R1 and R2 are independently selected from the group consisting of H, halo, -CF3, -OR10, -COR10, -SR10, -S(O)tR11 wherein t is 0,1 or 2, -SCN, -N(R10)2, -NR10R11, -NO2, -OC(O)R10, -C02R10, -OCO2R11, -CN, -NHC(O)R10, -NHSO2R10, -CONHR10, -CONHCH2CH2OH, -NR10COOR11, Formula II, -SR11C(O)OR11, -SR11N(R75)2, wherein each R75 is independently selected from H and -C(O)OR11, benzotriazol-1-yloxy, tetrazol-5-ylthio, substituted tetrazol-5-ylthio, alkynyl, alkenyl and alkyl, R3 and R4 are independently selected from the group consisting of H, R1 and R2, or R3 and R4 taken together represent a saturated or unsaturated C5-C7 fused ring to the benzene ring; R5, R6, R7 and R8 are independently selected from the group consisting of H, -CF3, -COR10, alkyl and aryl, and R10 represents H, alkyl, aryl, or aralkyl; X represents N, CH or C, which C may contain an optional double bond (represented by the dotted line) to carbon atom 11; the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently are selected from the group consisting of -R10, halo, -OR11, -OC02R11 and -OC(O)R10, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent (H, H), (OR11, -OR11), (H, halo), (halo, halo), (alkyl, H), (alkyl, alkyl), (H, -OC(O)R10), (H, -OR10), =O, (aryl, H) and =NOR10, or A and B together are -O-(CH2)p-O- wherein p is 2, 3 or 4; and R represents: (1) -C(O)N(R10)2; (2) -CH2C(O)N(R1 )2; (3) -SO2-alkyl, -SO2-aryl, -S02-aralkyl, -SO2-heteroaryl or -SO2 heterocycloalkyl; (4) cyano; (5) an imidate represented by the formula III; (6) an imidamido group of the formula IV; (7) a 1-amino-2-nitroethylene derivative of the formula V; (8) -C(O)R16; (9) -O(O)-O-R16; (10) Formula VI; (11) alkyl, aryl. aralkyl, cycloalkyl, heterocycloalkyl or heteroaryl; (12) -S02NR10R14; (13) -P(O)(R10)2; (14) a sugar group of the formula VII, VIII, IX; (15) -CH2C(O)OR28.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71332696A | 1996-09-13 | 1996-09-13 | |
| PCT/US1997/015900 WO1998011096A1 (en) | 1996-09-13 | 1997-09-11 | Tricyclic compounds useful for inhibition of g-protein function and for treatment of proliferative diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ334340A true NZ334340A (en) | 2000-09-29 |
Family
ID=24865700
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ334340A NZ334340A (en) | 1996-09-13 | 1997-09-11 | Tricyclic compounds that inhibits farnesyl protein transferase I but not geranylgeranyl protein transferase I in the treatment of cancer or cancer-like conditions |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP0927178B1 (en) |
| JP (1) | JP3152438B2 (en) |
| KR (1) | KR20000036059A (en) |
| CN (1) | CN1237169A (en) |
| AT (1) | ATE213736T1 (en) |
| AU (1) | AU729810B2 (en) |
| BR (1) | BR9712819A (en) |
| CA (1) | CA2264569C (en) |
| CZ (1) | CZ83499A3 (en) |
| DE (1) | DE69710741T2 (en) |
| ES (1) | ES2169420T3 (en) |
| HK (1) | HK1018267A1 (en) |
| HU (1) | HUP9904067A2 (en) |
| ID (1) | ID22045A (en) |
| IL (1) | IL128949A0 (en) |
| NO (1) | NO991230L (en) |
| NZ (1) | NZ334340A (en) |
| PL (1) | PL332240A1 (en) |
| SK (1) | SK33199A3 (en) |
| TR (1) | TR199900561T2 (en) |
| WO (1) | WO1998011096A1 (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6433165B1 (en) | 1998-01-21 | 2002-08-13 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US6509346B2 (en) | 1998-01-21 | 2003-01-21 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| DE69928226T8 (en) | 1998-01-21 | 2006-10-19 | Millennium Pharmaceuticals, Inc., Cambridge | CHEMOKIN RECEPTOR ANTAGONISTS AND USE |
| US6613905B1 (en) | 1998-01-21 | 2003-09-02 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US7271176B2 (en) | 1998-09-04 | 2007-09-18 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use thereof |
| US6503926B2 (en) | 1998-09-04 | 2003-01-07 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US6288083B1 (en) | 1998-09-04 | 2001-09-11 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| US7541365B2 (en) | 2001-11-21 | 2009-06-02 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| TWI291467B (en) | 2002-11-13 | 2007-12-21 | Millennium Pharm Inc | CCR1 antagonists and methods of use therefor |
| WO2005017160A2 (en) | 2003-08-13 | 2005-02-24 | Children's Hospital Medical Center | Mobilization of hematopoietic cells |
| RU2408584C2 (en) | 2005-06-23 | 2011-01-10 | Мерк Шарп Энд Домэ Корп. | Tyrosine kinase inhibitors |
| TW200813021A (en) | 2006-07-10 | 2008-03-16 | Merck & Co Inc | Tyrosine kinase inhibitors |
| TW201024283A (en) * | 2008-12-01 | 2010-07-01 | Targacept Inc | Synthesis and novel salt forms of (R)-3-((E)-2-(pyrrolidin-3-yl)vinyl)-5-(tetrahydropyran-4-yloxy)pyridine |
| EP3519385B1 (en) | 2016-09-27 | 2020-11-18 | Mission Therapeutics Limited | Cyanopyrrolidine derivatives with activity as inhibitors of usp30 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ274749A (en) * | 1993-10-15 | 1998-05-27 | Schering Corp | Tricyclic carbamate derivatives useful for inhibition of g-protein function and for treating proliferative diseases, medicaments |
| ATE210653T1 (en) * | 1993-10-15 | 2001-12-15 | Schering Corp | TRICYCLIC SULFONAMIDE DERIVATIVES FOR INHIBITING G-PROTEIN FUNCTION AND FOR THE TREATMENT OF PROLIFERATIVE DISEASES |
| IL111235A (en) * | 1993-10-15 | 2001-03-19 | Schering Plough Corp | Pharmaceutical compositions for inhibition of g-protein function and for treatment of proliferative diseases containing tricyclic compounds some such compounds and process for preparing part of them |
-
1997
- 1997-09-11 CZ CZ99834A patent/CZ83499A3/en unknown
- 1997-09-11 NZ NZ334340A patent/NZ334340A/en unknown
- 1997-09-11 EP EP97941474A patent/EP0927178B1/en not_active Expired - Lifetime
- 1997-09-11 JP JP51375998A patent/JP3152438B2/en not_active Expired - Fee Related
- 1997-09-11 KR KR1019997002062A patent/KR20000036059A/en not_active Application Discontinuation
- 1997-09-11 BR BR9712819-8A patent/BR9712819A/en unknown
- 1997-09-11 TR TR1999/00561T patent/TR199900561T2/en unknown
- 1997-09-11 ES ES97941474T patent/ES2169420T3/en not_active Expired - Lifetime
- 1997-09-11 ID IDW990090D patent/ID22045A/en unknown
- 1997-09-11 AU AU43373/97A patent/AU729810B2/en not_active Ceased
- 1997-09-11 WO PCT/US1997/015900 patent/WO1998011096A1/en not_active Application Discontinuation
- 1997-09-11 CA CA002264569A patent/CA2264569C/en not_active Expired - Fee Related
- 1997-09-11 DE DE69710741T patent/DE69710741T2/en not_active Expired - Fee Related
- 1997-09-11 PL PL97332240A patent/PL332240A1/en unknown
- 1997-09-11 IL IL12894997A patent/IL128949A0/en unknown
- 1997-09-11 SK SK331-99A patent/SK33199A3/en unknown
- 1997-09-11 HU HU9904067A patent/HUP9904067A2/en unknown
- 1997-09-11 AT AT97941474T patent/ATE213736T1/en not_active IP Right Cessation
- 1997-09-11 CN CN97199586A patent/CN1237169A/en active Pending
-
1999
- 1999-03-12 NO NO991230A patent/NO991230L/en not_active Application Discontinuation
- 1999-07-26 HK HK99103194A patent/HK1018267A1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CN1237169A (en) | 1999-12-01 |
| KR20000036059A (en) | 2000-06-26 |
| CA2264569C (en) | 2003-11-11 |
| WO1998011096A1 (en) | 1998-03-19 |
| EP0927178B1 (en) | 2002-02-27 |
| TR199900561T2 (en) | 1999-06-21 |
| NO991230L (en) | 1999-05-14 |
| AU4337397A (en) | 1998-04-02 |
| ATE213736T1 (en) | 2002-03-15 |
| AU729810B2 (en) | 2001-02-08 |
| ES2169420T3 (en) | 2002-07-01 |
| PL332240A1 (en) | 1999-08-30 |
| EP0927178A1 (en) | 1999-07-07 |
| IL128949A0 (en) | 2000-02-17 |
| DE69710741T2 (en) | 2002-10-24 |
| HK1018267A1 (en) | 1999-12-17 |
| SK33199A3 (en) | 1999-12-10 |
| NO991230D0 (en) | 1999-03-12 |
| ID22045A (en) | 1999-08-26 |
| CZ83499A3 (en) | 1999-07-14 |
| HUP9904067A2 (en) | 2000-05-28 |
| DE69710741D1 (en) | 2002-04-04 |
| JP2000502727A (en) | 2000-03-07 |
| JP3152438B2 (en) | 2001-04-03 |
| CA2264569A1 (en) | 1998-03-19 |
| BR9712819A (en) | 1999-11-23 |
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